Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 575 - 575

Опубликована: Янв. 11, 2025

Inflammatory bowel disease (IBD), encompassing Crohn's and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30-50% patients or cause significant side effects, emphasizing need new treatments. Targeting innate immune system enhancing drug delivery to inflamed gut regions promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) neutrophil extracellular traps (NETs) -DNA-based structures with cytotoxic proteins-that contribute mucosal damage inflammation. Recent studies linking ROS production, DNA repair, NET formation have identified NETs as potential therapeutic targets, preclinical models showing positive outcomes from inhibition. Innovative oral systems designed target directly-without systemic absorption-could improve treatment precision reduce effects. Advanced formulations utilize properties such particle size, surface modifications, ROS-triggered release selectively distal ileum colon. A dual strategy that combines deeper understanding pathophysiology identify inflammation-related targets advanced may offer promise. For instance, pairing inhibition ROS-responsive nanocarriers could enhance efficacy, though further research is needed. This synergistic approach has greatly patients.

Язык: Английский

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Diosmetin Inhibits NETs Formation in Neutrophils Through Regulating Nrf2 Signaling

Thoracic Cancer, Год журнала: 2025, Номер 16(6)

Опубликована: Март 1, 2025

Neutrophil extracellular traps (NETs) are important pieces of equipment for neutrophils. Excess NETs play promoting roles in cancer-associated thrombosis (CAT). Therefore, directing formation is a promising therapeutic strategy and related diseases. Diosmetin, an antioxidant flavonoid derived from dietary sources, might be involved CAT. Firstly, the tests cell-free DNA Immunofluorescence were applied to evaluate levels Luminol-based chemiluminescence DCFH-DA probe used detect reactive oxygen species (ROS) Then, network pharmacological analysis molecular docking predict potential target molecules diosmetin. The RT-qPCR was performed measure Nrf2 HO-1. A series functional assays neutrophils examine effect diosmetin on other neutrophil functions. Finally, animal model deep vein constructed assess thrombosis. Diosmetin reduced ROS mechanisms suggested that primary treatment increased HO-1 NETs-generating An inhibitor diminished negative generation. Lastly, murine results indicated via formation. exerts as anti-NETs through signaling neutrophils, showing thromboembolism pathological processes, such

Язык: Английский

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Advances in the Study of Sepsis-Induced ARDS

Advances in Clinical Medicine, Год журнала: 2025, Номер 15(02), С. 852 - 860

Опубликована: Янв. 1, 2025

Язык: Английский

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Neutrophils and COVID-19

Progress in molecular biology and translational science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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The emerging significance of furan fatty acids in Food, nutrition, and potential therapeutic use

Food Chemistry, Год журнала: 2025, Номер 479, С. 143759 - 143759

Опубликована: Март 8, 2025

Язык: Английский

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Macrophage membrane-coated polydopamine nanomedicine for treating acute lung injury through modulation of neutrophil extracellular traps and M2 macrophage polarization

Materials Today Bio, Год журнала: 2025, Номер unknown, С. 101708 - 101708

Опубликована: Март 1, 2025

Язык: Английский

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Giardia duodenalis triggered neutrophil extracellular traps in goats

Immunobiology, Год журнала: 2025, Номер 230(3), С. 152894 - 152894

Опубликована: Март 29, 2025

Giardia duodenalis is a globally distributed zoonotic parasite primarily transmitted through the fecal-oral route, infecting various vertebrates, and infection of which prevalent in goats. Immune cells play crucial role pathogens invasion, neutrophil extracellular traps (NETs) released by neutrophils serve as non-specific defense mechanism against including parasites. In this study, we investigated characteristics, components, molecular mechanisms goat NETs upon stimulation with G. trophozoites. This study demonstrates that trigger dose-dependent formation neutrophils, composed DNA, citrullinated histone H3 (CitH3), elastase (NE). Reactive oxygen species (ROS) accumulation synchronizes NETosis during infection. Inhibitor experiments confirmed duodenalis-induced ROS production depend on TLR2/4 signaling require NADPH oxidase (NOX), ERK1/2, p38 MAPK activation. work identifies TLR2/4, NOX, pathways key regulators NETs/ROS coordination infection, providing first evidence duodenalis-triggered The findings highlight critical components anti-G. immunity suggest potential for NETs-targeted therapeutic strategies.

Язык: Английский

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Sex and Genotype Affect Mouse Hippocampal Gene Expression in Response to Blast-Induced Traumatic Brain Injury

Molecular Neurobiology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Blast-induced traumatic brain injury (bTBI) has been identified as an increasingly prevalent cause of morbidity and mortality in both military civilian populations over the past few decades. Functional outcomes following bTBI vary widely among individuals, chronic neurodegenerative effects including cognitive impairments can develop without effective diagnosis treatment. Genetic predispositions sex differences may affect gene expression changes response to influence individual's probability sustaining long-term damage or exhibiting resilience tissue repair. Male female mice from eight genetically diverse distinct strains (129S1/SvImJ, A/J, C57BL/6J, CAST/EiJ, NOD/ShiLtJ, NZO/HlLtJ, PWK/PhJ, WSB/EiJ) which encompassed 90% genetic variability commercially available laboratory were exposed a single (180 kPa) using well-established shock tube system. Subacute hippocampal due blast exposure assessed RNA-seq at 1-month post-injury. We patterns dysregulation ontology terms canonical pathways related mitochondrial function, ribosomal structure, synaptic plasticity, protein degradation, intracellular signaling that varied by and/or strain, significant genes encoding respiratory complex I electron transport chain male WSB/EiJ glutamatergic synapse across more than half our groups. This study represents multi-level examination how provides foundation for identification potential therapeutic targets could be modulated improve health Veterans others with histories exposures.

Язык: Английский

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Mitochondrial DNA signals driving immune responses: Why, How, Where?

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 22, 2025

Abstract There has been a recent expansion in our understanding of DNA-sensing mechanisms. Mitochondrial dysfunction, oxidative and proteostatic stresses, instability impaired disposal nucleoids cause the release mitochondrial DNA (mtDNA) from mitochondria several human diseases, as well cell culture animal models. mislocalized to cytosol and/or extracellular compartments can trigger innate immune inflammation responses by binding receptors (DSRs). Here, we define features that make mtDNA highly immunogenic mechanisms its into compartments. We describe major DSRs bind such cyclic guanosine-monophosphate-adenosine-monophosphate synthase (cGAS), Z-DNA-binding protein 1 (ZBP1), NOD-, LRR-, PYD- domain-containing 3 receptor (NLRP3), absent melanoma 2 (AIM2) toll-like 9 (TLR9), their downstream signaling cascades. summarize key findings, novelties, gaps driving signal vascular, metabolic, kidney, lung, neurodegenerative viral bacterial infections. Finally, common strategies induce or inhibit propose challenges advance field.

Язык: Английский

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Interplay between the gut microbiota, its metabolites and carcinogens

Clinical & Translational Oncology, Год журнала: 2025, Номер unknown

Опубликована: Май 13, 2025

Язык: Английский

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